The antioxidant uncoupling protein 2 stimulated hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes páncreas cancer cells to glycolysis inhibition

Show simple item record Brandi, J. Cecconi, D. Cordani, M. Torrens-Mas, M. Pacchiana, R. Dalla Pozza, E. Butera, G. Manfredi, M. Marengo, E. Oliver, J. Roca, P. Dando, I. Donadelli, M. 2024-02-07T07:44:04Z
dc.description.abstract Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes. In particular, we demonstrate that the antioxidant UCP2 induces the expression of hnRNPA2/B1, which is involved in the regulation of both GLUT1 and PKM2 mRNAs, and of lactate dehydrogenase (LDH) increasing the secretion of L-lactic acid. We further demonstrate that the radical scavenger N-acetyl-L-cysteine reverts hnRNPA2/B1 and PKM2 inhibition by genipin indicating a role for reactive oxygen species in the metabolic reprogramming of cancer cells mediated by UCP2. We also observe an UCP2-dependent decrease in mtOXPHOS complex I (NADH dehydrogenase), complex IV (cytochrome c oxidase), complex V (ATPase) and in mitochondrial oxygen consumption, suggesting a role for UCP2 in the counteraction of pancreatic cancer cellular respiration. All these results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation with the concomitant metabolic shift from mtOXPHOS to the glycolytic pathway.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Free Radical Biology and Medicine, 2016, vol. 101, p. 305-316
dc.subject.classification 57 - Biologia
dc.subject.classification Ciències de la salut
dc.subject.other 57 - Biological sciences in general
dc.subject.other Medical sciences
dc.title The antioxidant uncoupling protein 2 stimulated hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes páncreas cancer cells to glycolysis inhibition
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2024-02-07T07:44:04Z info:eu-repo/date/embargoEnd/2100-01-01
dc.embargo 2100-01-01
dc.subject.keywords Cancer
dc.subject.keywords metabolism
dc.subject.keywords proteomics
dc.subject.keywords UCP2
dc.subject.keywords Warburg effect
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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